Non-invasively measuring arterial oxygen tension

ABSTRACT

Oxygen tension is measured in the palpebral conjuctiva and is converted to arterial oxygen tension by applying a conversion factor thereto. A polarographic oxygen sensor on the outer surface of a scleral contact member is employed, and the current passed is read and converted, or read in terms of a special calibration.

The invention described herein was made in the course of a grant fromthe Department of Health, Education and Welfare.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of application Ser. No.273,422 filed July 20, 1972, now abandoned.

BACKGROUND OF THE INVENTION

This invention relates to non-invasive and continuous measurement ofarterial oxygen tension.

Arterial oxygen tension or partial pressure and its changes arephenomena with great significance in several fields of medicine,including anesthesiology, treatment of respiratory diseases, andtreatment of prematurely born infants. It is very valuable to knowexactly what this tension is and to know it continuously and currently.Invasive techniques, such as the analysis of blood samples may overlyweaken the patient and in any event cannot give either current orcontinuous knowledge. The best and quickest analysis of a blood sampleconsumes several minutes, especially where the laboratory and thepatient are a few minutes apart; it can never provide continuousmonitoring.

Attempts to predict or determine arterial oxygen tension indirectly frommeasured tissue oxygen tension have not heretofore yielded anyclinically useful methods. When polarographic oxygen sensors are pressedagainst tissues, such as the skin, the mucous membranes of the mouth,the cornea, or the bulbar conjunctiva, there is no finite steady-stateoxygen tension; instead, the recorded oxygen tension falls rapidly tozero. Even after several years of research and development thenon-invasive oximeter, which measures oxyhemoglobin saturation ratherthan oxygen tension, is still not widely used as a monitoring device. Inparticular, it does not help monitor hyperoxic states.

The present invention is capable of continuously monitoring arterialoxygen tension. It can measure arterial oxygen tension in both hyperoxicand hypoxic states and is not limited by the 100% saturation ofhemoglobin as is the oximeter.

The invention enables an anesthetist to observe the instant effect ofdecreasing and increasing inspired oxygen tension and ventilation.

When ventilation is assisted in chronic and acute respiratory disease,there is need for evaluating the state of respiration; in addition todata such as tidal volume, blood oxygen tension provided by the presentinvention can be helpful.

A third immediate area of great usefulness of the present invention isin the premature nursery. For example, isolette oxygen tensions can beadjusted by feedback from a device embodying the invention, chronicpalpebral conjunctival electrode taped under one eyelid. Eithercontinuous or sporadic non-invasive, non-blood loss evaluation ofarterial PO₂ can be made.

In the area of chronic lung disease a chest internist can use theinvention as a diagnostic tool when correlated with certain simplespirometer measurements. In many instances, the non-invasive nature ofthe test of the present invention is more acceptable on an out-patientbasis than arterial puncture.

In the diagnosis and evaluation of shock this invention is capable ofgreater sensitivity than a sphygmomanometer. The organism tries tomaintain its blood pressure and arterial oxygen tension; however, tissueperfusion and oxygenation, especially to non-critical areas, may beaffected very easily.

SUMMARY OF THE INVENTION

This invention rests on my discovery that arterial oxygen tension can bedetermined by determining the oxygen tension of the palpebralconjunctiva. These two tensions are not the same, nor can a time factorbe completely disregarded, but they are so closely related that, forexample, by multiplying the palpebral conjunctival oxygen tension by aconstant that depends on the type of organism and then subtracting asecond constant, the arterial oxygen tension is obtained. Only a shortdelay time is involved, for the palpebral conjunctival oxygen tensionadjusts quickly to any change in arterial oxygen tension.

This discovery has been described in a published paper by Marcus Kwanand Irving Fatt entitled "A Noninvasive Method of Continuous ArterialOxygen Tension Estimation from Measured Palpebral Conjunctival OxygenTension", printed in Vol. 35, No. 3, of Anesthesiology, September 1971,pages 309-314.

The palpebral conjunctiva is a very specialized tissue. The avascularcornea of the open eye obtains almost all of its oxygen from theatmosphere. When the eye is closed, about a third of the oxygen neededby the cornea comes from the aqueous humor, and about two-thirds fromthe conjunctival capillaries. The vessels of the palpebral conjunctivaare so close to the conjunctival epithelium that they are clearlyvisible. The mucous membrane epithelium overlying these vessels is onlytwo to four cell layers thick, and appears to have a very low oxygenconsumption rate. The palpebral conjunctiva, therefore, is an easilyaccessible capillary bed not covered by a thick layer ofoxygen-consuming tissue.

A suitable polarographic oxygen sensor, such as an electrode assembly,is mounted on a scleral contact lens or lens segment and used to measurepalpebral conjunctival tissue gas tensions either continuously orsporadically, as desired. The palpebral conjunctiva supplies oxygen, forexample, to the cornea when the eyelids are shut, thus providing aunique opportunity to separate, atraumatically, a capillary bed with ahigh oxygen tension from its oxygen-consuming tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings:

FIG. 1 is a view in cross-section of a portion of an eye and uppereyelid with an electrode-carrying scleral contact lens installed,according to the principles of the invention.

FIG. 2 is a view in side elevation of a scleral contact lensincorporating an oxygen-sensing electrode in accordance with theinvention.

FIG. 3 is a fragmentary view in section of a portion of the assembly ofFIG. 2.

FIG. 4 is a circuit diagram for a gas electrode circuit.

FIG. 5 is a tracing of palpebral conjunctival oxygen tension over aperiod of time, with various changes in oxygen ratio in the gas beingbreathed.

FIG. 6 is a graph showing a typical relationship between palpebralconjunctival oxygen tension and arterial oxygen tension, plotting oxygentension in torrs against inspired oxygen tension in torrs.

FIG. 7 is a graph of mean arterial oxygen tension versus mean palpebralconjunctival oxygen tension at a series of inspired oxygen tensions.

DESCRIPTION OF A PREFERRED EMBODIMENT

FIG. 1 shows an eye 10 having an eyelid 11 with a palpebral conjunctiva12. The eye 10 has a cornea 13. According to the present invention, theoxygen tension of the palpebral conjunctiva is to be sensed andmeasured. This is done by inserting a scleral contact lens 15 over thecornea 13, the lens 15 having an inner surface 16 in contact or partialcontact with the cornea 13 and an outer surface 17 in contact with thepalpebral conjunctiva 12.

As shown in FIGS. 2 and 3 this contact lens 15 is provided with at leastone sensor 20, which may comprise a Clark polarographic oxygen electrodesensor, having a silver anode 21 and a small platinum cathode 22embedded in plastic 23 and covered by a thin film or membrane 24 ofmaterial such as 12μ polyethylene. The sensor 20 may be secured to theouter surface 17.

The sensor 20 has leads 25 and 26. As shown in FIG. 4, the lead 25 fromthe anode 21 may be grounded and pass to a suitable microammeter 27 andto a recorder 28. The lead 26 from the cathode 22 may go to a voltagedivider 30 comprising two resistors 31 and 32, and a power source 33,such as a 1.35 volt cell may be converted to opposite ends of thevoltage divider 30, which is connected by a lead 34 to the ammeter 27.Other types of circuits may be used.

Continuous measurements of palpebral conjunctival oxygen tensions havebeen obtained by such a membrane-covered (polyethylene, 12μ)polarographic electrode 20 with a platinum cathode 22 that was 25μ indiameter mounted eccentrically on a scleral contact lens 15. The site ofattachment was chosen so that the electrode 20 would abut directly onthe tarsal portion of the palpebral conjunctiva 12, where the epithelialtissue is firmly stretched over a supporting structure of denseconnective tissue and where the epithelium would normally be in contactwith the cornea 13 when the eye 10 is closed. One particular electrodeor sensor 20 in the finished state produced a small protuberance (2.0 to2.5 mm at the most) of the lid 11 above the normal curvature of the eye10 covered by the scleral contact lens 15.

The electronic circuitry for the conjunctival electrode may compriseprimarily a Hewlett-Packard microammeter 27 and a Heathkit.[.sevo-recorder.]. .Iadd.servo-recorder .Iaddend.28. Between thecathode 22 and the silver anode 21, a potential of 0.75 volts wasapplied by the cell 33. In this system currents of 2 to 3 nanoamps wererecorded for 150 torr oxygen. To check correlation, arterial oxygentension measurements were also done on blood samples taken from thefemoral artery and passed over a standard Clark polarographic oxygensensor in a constant-temperature cuvette. A Beckman Model 160 gasanalyzer was used for readout. Blood pressure was monitored via acatheter in the femoral artery and a Model P2- 1251 Wiancko pressuretransducer.

The contact-lens electrode 20 was calibrated at 35°-36° C. Thetemperature under the eyelid 11, measured by a small polyethylenethermistor probe, remained in the range of 37.0° to 36.4° C. during afour-hour experiment. The arterial electrode was calibrated andmaintained at 39° C. Water-saturated pure nitrogen and water-saturatedair were used as standards.

In animal tests, eight adult New Zealand White rabbits were anesthetizedwith 40 to 50 mg/kg of sodium pentobarbital of 2.0 g/kg of urethane individed doses so that the corneal reflexes were lost. Tracheostomieswere performed, and the rabbits allowed to respire at their own ratesand depths. A polyethylene cannula was placed in a femoral artery andthreaded into the distal aorta to take arterial samples and monitorblood pressure.

The scleral contact-lens 15 with the oxygen electrode 20 was thenpositioned in the eye of the rabbit and the lid sutured shut. Sutureswere used for these tests because tape would not stick to the hairyrabbit eyelids; in one rabbit, however, tape was sufficient to hold theelectrode in place. The palpebral conjunctival oxygen tensions wererecorded continuously with the rabbits inspiring various mixtures ofoxygen, prepared by mixing 100 per cent oxygen and 100 per cent nitrogenthrough two flowmeters, two feet of tubing and a rebreathing bag. Insome experiments, at each inspired oxygen tension an arterial bloodsample was taken and its oxygen tension measured after the conjunctivaloxygen tension had become stable. Recalibration at the termination ofthe experiment showed that the contact-lens electrode 20 was stableafter five hours.

As shown graphically in FIG. 5, within one-half to two minutes afterchanging the composition of the inspired oxygen mixture, a maximal andsteady-state tissue oxygen tension was found. Stable repeatable tissueoxygen tensions varying from 35 to 520 torr were obtained continuouslyover a three to five-hour period in each of eight experiments for arange 10 to 100 per cent inspired oxygen. No variation in electrodecurrent was caused by the mechanical pressures generated by the eyelidsover the electrode face. Movement of the contact-lens electrode underthe lid for distances of 5 to 6 mm resulted in transient changes incurrent, but the oxygen tension recorded returned to the precedingstable reading once the movement stopped. Thus, the time delay betweenbreathing and palpebral conjuctival oxygen tension is quite brief, andthe delay with respect to arterial oxygen is even shorter.

When the rabbits were breathing room air, palpebral conjuctival oxygentensions of 50 to 100 torr were obtained. On the basis ofoxygen-hemoglobin dissociation data in the rabbit, the expected arterialoxygen tension would be 75 to 80 torr at 95 percent saturation. Theexperimental results for both tissue and arterial oxygen tensions (seeFIG. 6) are in good agreement with this expectation for respiration ofroom air. Mean conjuctival-tissue PO₂ was 70 ± 13.3 torr, and meanarterial PO₂ 93 ± 13.4 torr when room air was inspired. Charleton, Read,and Read (in Journal of Applied Physiology, Volume 18, No. 6, pages1247-1251, 1963) reported that intraarterial oxygen tensions measured bya microelectrode in man varied from 70 to 127 torr (mean 84 torr) duringrespiration of air at rest; with voluntary hyper-ventilation of 712 torroxygen, arterial oxygen tensions varied from 610 to 656 torr (mean 637torr).

The steady-state palpebral conjuctival oxygen tensions recorded and thearterial oxygen tensions are shown in FIG. 6 as functions of a widerange of inspired oxygen tensions.

One mounted membrane-covered electrode 20 protruded 2.0-2.5 mmvertically from the carrier lens 15 and with an O-ring 35 in placeproduced a 6-7 mm circular, horizontal protuberance. Fine insulated wireleads 26 and 25 connect the electrode 20 to the battery box whichprovides the polarizing voltage. The polyethylene-covered cathode 22 andanode 21 thus are insulated from the body and should not add to themicrocurrents involved in EKG monitoring or the macrocurrents fromelectrocautery. The battery box is connected to the microammeter 27 andrecorder 28 which may rest on a cart or other support close to thesubject's head. These instruments 27 and 28 are suitably calibrated, asdescribed below. A calibrating setup including a constant temperaturebath, and small tanks of gas may also be included in this space.

Operator skills required are essentially the same as those required foranyone making arterial blood gas measurements.

Human trials have employed an electrode 20 mounted on a corneal contactlens 15. In normovolemic, normotensive, anesthetized patients, the sametype of correlation exists between palpebral conjunctival PO₂ andarterial PO₂ as in the rabbit. Standard deviations are even smaller,perhaps because of the much better control of perfusion, ventilation andanesthesia.

The estimating equation (arterial PO₂ = 34.4+0.91 × inspired PO₂) forarterial PO₂ as a function of inspired PO₂ is represented by the uppersolid line in FIG. 6 and has a correlation coefficient, r, of 0.98. Onestandard deviation of the .[.estimated arterial Po₂,.]. .Iadd.estimatedarterial PO₂ .Iaddend. for the entire line is 30 torr. The lower solidline in FIG. 6 represents the estimating equation (tissue PO₂ = 17.8 +0.40 × inspired PO₂) for tissue PO₂ as a function of inspired PO₂, r is0.67, and one standard deviation for the entire line is 68 torr. The twolines in FIG. 6 show that the palpebral conjunctival oxygen tension asmeasured in this system can give an approximation of the arterial oxygentension.

The relationship between .[.palpegral.]. .Iadd.palpebral.Iaddend.conjunctival and arterial .[.oxyten.]. .Iadd.oxygen.Iaddend.tensions for any given inspired oxygen tension is given by theequation: arterial PO₂ = 2.3 × palpebral conjunctival PO₂ -- 75 torr.Arterial PO₂ can be estimated from a measured tissue PO₂ graphically, ifdesired. For any inspired PO₂ a correction factor can be added to themeasured palpebral conjunctival tissue PO₂ to give an estimate ofarterial PO₂. FIG. 7 is a graph of the mean arterial PO₂ versus the meanconjunctival PO₂ at each inspired oxygen tension, and again reflects thelinear correlation between the two. Part of the deviation from atheoretical 1:1 correlation indicates the extent of oxygen consumptionby the tissue between sensor and the capillaries; the rest is probablydue to relative decreases in local blood flow at higher oxygen tensions.

The ammeter 27 and recorder 28 are preferably calibrated to readarterial PO₂ directly by an appropriate readout scale to provide themultiplier constant of the above equation, while the location of thezero point provides the subtraction constant. This calibration therebymultiplies the detected tension by the indicated constant while alsosubtracting a second constant. The spread of the calibration points thusaccomplishes multiplication, and the location of zero therein effectssubtraction -- in just the same manner as any ammeter (e.g., agalvanometer) may be calibrated to read in terms of amperes,milliamperes, or microamperes and may be calibrated to read in terms ofcurrent above any predetermined level. Here the ammeter 27 and recorder28 may be calibrated either in terms of palpebral oxygen tension or interms of arterial oxygen tension.

This system is apparently capable of monitoring hypoxic and hyperoxicstates, and gives an estimate of arterial oxygen tension innormotensive, normovolemic animals. The conjunctival electrode, which isnot limited by the 100 percent saturation of hemoglobin, can be veryuseful as a means of detecting hyperoxia in premature infant nurseriesand acute pulmonary .[.case centers..]. .Iadd.care centers. .Iaddend.Themonitoring system of this invention may show a characteristic dependenceof tissue oxygen tension on local blood flow, which could make thepalpebral conjunctival electrode useful as a signal of impending shock.This technique has the additional advantage of being non-invasive andrelatively atraumatic. No gross corneal damage was noted in the rabbits,and scleral contact lenses have been in human use for years.

Because of the rapid response (minutes), the stability (hours), and thesteady-state nature at a given oxygen tension, this conjunctivalmonitoring system is well suited to use as an aid in the continuousmonitoring of the levels of oxygenation of patients during anesthesiaand intensive respiratory care. The palpebral conjunctiva is supplied bythe internal carotid artery via branches of the ophthalmic artery, andthus may be preferentially perfused over other cutaneous areas duringminimal hypovolemia. Preliminary studies show that for animals in shockthe palpebral conjunctival oxygen tension has a more complexrelationship to the arterial oxygen tension. Once the exact relationshipis better understood, this monitoring device will have further clinicaluse.

Thus, this invention is adapted to human use as a non-invasive,continuous method for monitoring arterial oxygen tensions.

To those skilled in the art to which this invention relates, manychanges in construction and widely differing embodiments andapplications of the invention will suggest themselves without departingfrom the spirit and scope of the invention. The disclosures and thedescription herein are purely illustrative and are not intended to be inany sense limiting.

I claim:
 1. A method for non-invasively determining continuous arterialoxygen tension of a patient, comprising the steps ofa. non-invasivelymeasuring the palpebral conjunctival oxygen tension, b. multiplying saidtension by a constant dependent upon the relationship between the oxygentension of the palpebral conjunctiva and the arterial oxygen tension ofthe patient, and c. subtracting a second constant also dependent uponsaid relationship.
 2. The method of claim 1 wherein said measuring,multiplying and subtracting are carried out substantially simultaneouslyand continuously.
 3. A method for non-invasively and continuouslydetermining continuous arterial oxygen tension of a patient, comprisingthe steps ofa. continuously non-invasively measuring the palpebralconjunctival oxygen to provide readings thereof; and b. continuouslyconverting the readings to values in terms of the relation of palpebralconjunctival readings to arterial conditions.
 4. The method of claim 3wherein the measurements are continuously recorded.
 5. A method fornon-invasively determining continuous arterial oxygen tension of apatient, comprising the steps of1. securing an oxygen-sensing electrodeassembly to the outer surface of a scleral contact lens member, 2.emplacing said contact lens member between the cornea of the patient'seye and the palpebral conjunctiva of his eyelid,
 3. applying voltage tosaid electrode assembly,
 4. reading the current passed, and 5.calibrating said current in terms of the oxygen tension modified byfactors corresponding to the relation between the slope and origin ofthe arterial oxygen tension to palpebral conjunctival oxygen tension. 6.The method of claim 5 wherein steps (3) and (4) are done continuously.7. The method of claim 6 wherein the calibrated reading is continuouslyrecorded.
 8. Apparatus for non-invasively determining arterial oxygentension of a patient, comprisinga. means to abut the surface ofpalpebral conjunctiva for detecting the oxygen tension thereof, b. meansfor reading the value of the detected tension while multiplying thisvalue by a constant dependent upon the type of patient and upon therelationship between oxygen tension of the palpebral conjunctiva and thearterial tension of the type of patient while subtracting a secondconstant also dependent on said relationship.
 9. The apparatus of claim8 wherein said means (a) comprise a membrane polarographic oxygensensor.
 10. Apparatus for non-invasively determining continuous arterialoxygen tension of a patient, comprisinga. means to abut the surface ofpalpebral conjunctiva for continuously detecting the oxygen tensionthereof, b. means for continuously indicating the value of the detectedtension while multiplying this value by a first constant dependent uponthe relationship between the oxygen tension of the palpebral conjunctivaand the arterial oxygen tension of the patient, and while continuouslysubtracting therefrom a second constant also dependent on saidrelationship, and c. means for continuously displaying the results of(b).
 11. Apparatus for non-invasively determining continuous arterialoxygen tension of a patient, comprising1. a scleral contact lens memberhaving an oxygen-sensing electrode assembly secured to said lens memberand sensing at the outer surface thereof, so that said contact lensmember can be placed between the cornea of the patient's eye and hiseyelid,
 2. means for applying voltage to said electrode,
 3. means forreading the current passed, and
 4. means calibrating said reading interms of the oxygen tension as modified by factors corresponding to therelation between the slope and origin of the arterial oxygen tension topalpebral conjunctival oxygen tension.
 12. The apparatus of claim 11wherein said gas-sensing electrode assembly is a membrane polarographicelectrode assembly. .Iadd.
 13. Apparatus for non-invasively indicatingcontinuous arterial oxygen tension of a patient, comprising1. a scleralcontact lens member having an oxygen-sensing electrode assembly securedto said lens member and sensing at the outer surface thereof, so thatsaid contact lens member can be placed between the cornea of thepatient's eye and his eyelid,
 2. means for applying voltage to saidelectrode,
 3. means for sensing the current passed, and
 4. meansindicating said sensed current in relation to the oxygen tension asmodified by factors corresponding to the relation between the slope andorigin of the arterial oxygen tension to palpebral conjunctival oxygentension. .Iaddend..Iadd.
 14. A method for non-invasively indicatingcontinuous arterial oxygen tension of a patient, comprising the stepsof
 1. securing an oxygen-sensing electrode assembly to the outer surfaceof a scleral contact lens member,
 2. emplacing said contact lens memberbetween the cornea of the patient's eye and the palpebral conjunctiva ofhis eyelid,
 3. applying voltage to said electrode assembly,
 4. sensingthe current passed, and
 5. indicating said sensed current in terms ofthe oxygen tension modified by factors corresponding to the relationbetween the slope and origin of the arterial oxygen tension to palpebralconjunctival oxygen tension. .Iaddend.